Overview of Male Reproductive Pathology

Abstract

An understand ing of form and function is important for exam ination of the m ale reproductive tract. A basic understand ing of spermatogenesis and horm onal function in the reproductive tract is essential for the pathologists in this evaluation. Gross and histologic reproductive changes need to be distinguished from normal variation and correlated with the reproductive status of the animal. This is especially important when correlating histologic changes with organ weight and other reproductive parameters, such as seminal analysis data. Sexual maturity of animals and tissue handing can impact interpretation. Sexual imm aturity of preclinical safety animals can present challenges for accurate identi cation of compound-related changes. Likewise, proper handlin g of un xed reproductive tissues and appropriate selection of a xation protocol are important in avoiding artifacts that may interfere with the microscop ic evaluation. The histopathology technician needs to recognize testicular landmark s that allow for correct orientation at trim ming so the pathologist can assess not only the morphology of sem iniferous tubules but also the out ow tract. For the m ost effective evaluation of the male reproductive tract, the testes and epididymides should be examine d concurrently. Although the term ''staging'' is often used inappropriately, the pathologist should review testicular tissues in a ''stage-aware'' manner. This article reviews gross and histologic changes of the m ale reproductive tract as well as tissue orientation and xation to assist in accurate interpretation of potential treatm ent-related change s in m ale reproduction.

Proliferative and Nonproliferative Lesions of the Rat and Mouse Male Reproductive System

“…Unilateral and bilateral tubular degeneration/atrophy may be seen as a low incidence, background finding in rats and mice. A common incidental finding in rat and mouse testes is the presence of a few (e.g., 1-5) atrophic tubular profiles lined only by Sertoli cells (Foley 2001). If these are recorded, it is important that they be distinguished from the more generalized distribution of tubular degeneration/atrophy described above.…”

“…Sperm stasis is occasionally seen as an incidental finding in rats and mice, particularly in atrophic tubules of aged mice. When sperm stasis occurs within the rete and causes obstruction of outgoing seminiferous tubule fluid, it can lead to tubule dilation and tubule atrophy, as described following administration of theophylline (Foley 2001 The following terms are recommended for changes of the testis related to specific germ cell types and/or stages, usually associated with shorter duration (up to 28 days) compound administration. They also can be seen as occasional background changes, but this is uncommon in the rat.…”

“…Pathogenesis: the consequence of germ cell degeneration, which may be mediated through Sertoli cell injury, primary cytotoxicity, hypoxia, inflammation, or other effects Diagnostic features (may include any combination of the following) Germ cell degeneration (individual germ cells with eosinophilic cytoplasm and nuclear condensation), not restricted to a specific germ cell type or stage Multinucleated germ cells Spermatid retention Sertoli cell cytoplasmic vacuolation Disorganization of germ cells Exfoliation of germ cells into tubular lumen Segmental partial germ cell loss Degenerate germ cells and debris present in the epididymis Generally associated with reduced organ weight Differential diagnoses Atrophy, tubular: majority of tubules depleted of most or all germ cells, leaving tubules mostly lined by Sertoli cells Degeneration, germ cell: largely restricted to a specific cell type and/or a specific tubular stage; generally seen as a compound-related change in studies less than 28 days duration Fixation artifact: germ cell dissociation and sloughing of cells into the lumen without seminiferous epithelial architectural disorder and without cell debris or sloughed cells in the epididymis; generally subcapsular Handling artifact: architectural disorder and/or sloughing of germ cells into the lumen without germ cell degeneration; generally affects few tubules in the subcapsular region; no sloughed germ cells or debris in the epididymis (Foley 2001) Necrosis, tubular: coagulative necrosis of seminiferous epithelium including Sertoli cells; inflammation may be present Autolysis: generalized dissociation of the Sertoli and germ cells with clumping and margination of nuclear chromatin; no cell debris or sloughed cells in the epididymis. (Bryant and Boekelheide 2007).…”

“…The reader is referred to the trimming protocols in goRENI (Kittel et al 2004) and Boorman, Chapin, and Mitsumori (1990) ;Boorman, Elwell, and Mitsumori (1990); Foley (2001);andSuwa et al (2001, 2002).…”

“…Proper microscopic assessment of testicular tissue in toxicity studies requires use of sexually mature animals, appropriate fixation, sampling and processing (Foley 2001;Lanning et al 2002;Latendresse et al 2002;Kittel et al 2004), and an understanding of spermatogenesis and its histologic presentation in the species under consideration ).…”